{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:14:08Z","timestamp":1791872048138,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014212","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss National Foundation","award":["PR00P3_208568"],"award-info":[{"award-number":["PR00P3_208568"]}]},{"name":"Fondation priv\u00c3\u00a9e des HUG","award":["RC09-18"],"award-info":[{"award-number":["RC09-18"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    , one of the leading causes of diarrheal death in children, remodels its infection site through secreted effector proteins. Several of them accumulate at the host-parasite interface, forming a complex structure whose function and importance for infection remain poorly understood. Here, we localized and functionally characterized the putative dense granule protein DG8. We confirmed the protein to be in the dense granules, forming a ring structure once secreted at the host-parasite interface. Deletion of DG8 showed reduced infection in mice\n                    <jats:italic>in vivo<\/jats:italic>\n                    and early defect\n                    <jats:italic>in vitro<\/jats:italic>\n                    , revealing the importance of DG8 for parasite fitness. Additional secreted proteins were identified as potential partners, among which SG4, a small granule protein, was shown to partially co-localize with DG8. Applying ultrastructure expansion microscopy on intestinal sections with newly generated antibodies against DG8 and SG4, we could precisely position the ring structure above the electron-dense band, around the feeder organelle at the base of the parasitophorous vacuole membrane with an unprecedent resolution. Altogether, better visualization and understanding of the host-parasite interface through expanded intestinal tissue and effectors characterization reveal a complex and essential layered host-parasite interface.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014212","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T17:52:53Z","timestamp":1778781173000},"page":"e1014212","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cryptosporidium secreted proteins form a complex layered interface with the host cell"],"prefix":"10.1371","volume":"22","author":[{"given":"Annet","family":"Puthenpurackal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Moreno Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tifany","family":"Schaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9na","family":"Falconnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyue","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Vadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8307-5099","authenticated-orcid":true,"given":"Amandine","family":"Gu\u00e9rin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"issue":"4","key":"ppat.1014212.ref001","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1556\/1886.2019.00019","article-title":"Cryptosporidium infection: epidemiology, pathogenesis, and differential diagnosis","volume":"9","author":"E Gerace","year":"2019","journal-title":"Eur J Microbiol Immunol (Bp)"},{"issue":"7","key":"ppat.1014212.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/S2214-109X(18)30283-3","article-title":"Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study","volume":"6","author":"IA Khalil","year":"2018","journal-title":"Lancet Glob Health"},{"issue":"5","key":"ppat.1014212.ref003","article-title":"The burden of cryptosporidium diarrheal disease among children < 24 months of age in moderate\/high mortality regions of Sub-Saharan Africa and South Asia, utilizing data from the Global Enteric Multicenter Study (GEMS)","volume":"10","author":"SO Sow","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1014212.ref004","article-title":"Case-control study of Cryptosporidium transmission in Bangladeshi households","author":"PS Korpe","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"7","key":"ppat.1014212.ref005","article-title":"Cryptosporidiosis should be designated as a tropical disease by the US food and drug administration","volume":"14","author":"RKM Choy","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"ppat.1014212.ref006","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s12639-022-01510-5","article-title":"An update on Cryptosporidium biology and therapeutic avenues","volume":"46","author":"AK Dhal","year":"2022","journal-title":"J Parasit Dis"},{"key":"ppat.1014212.ref007","doi-asserted-by":"crossref","first-page":"100542","DOI":"10.1016\/j.ijpddr.2024.100542","article-title":"Treating cryptosporidiosis: a review on drug discovery strategies","volume":"25","author":"A-C Leni\u00e8re","year":"2024","journal-title":"Int J Parasitol Drugs Drug Resist"},{"issue":"4","key":"ppat.1014212.ref008","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.chom.2020.09.007","article-title":"The biology of the intestinal intracellular parasite Cryptosporidium","volume":"28","author":"A Gu\u00e9rin","year":"2020","journal-title":"Cell Host Microbe"},{"issue":"4","key":"ppat.1014212.ref009","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1086\/315033","article-title":"Virulence of three distinct Cryptosporidium parvum isolates for healthy adults","volume":"180","author":"PC Okhuysen","year":"1999","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1014212.ref010","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s40588-021-00159-7","article-title":"Cryptosporidium: host-parasite interactions and pathogenesis","volume":"8","author":"DJ Pinto","year":"2021","journal-title":"Curr Clin Microbiol Rep"},{"issue":"5","key":"ppat.1014212.ref011","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.pt.2022.01.006","article-title":"Parasitology meets cryo-electron tomography - exciting prospects await","volume":"38","author":"LM Theveny","year":"2022","journal-title":"Trends Parasitol"},{"issue":"5","key":"ppat.1014212.ref012","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.13018","article-title":"Biogenesis and secretion of micronemes in Toxoplasma gondii","volume":"21","author":"DJ Dubois","year":"2019","journal-title":"Cell Microbiol"},{"issue":"3","key":"ppat.1014212.ref013","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/mmi.14674","article-title":"Biogenesis and discharge of the rhoptries: Key organelles for entry and hijack of host cells by the Apicomplexa","volume":"115","author":"R Ben Chaabene","year":"2021","journal-title":"Mol Microbiol"},{"issue":"6","key":"ppat.1014212.ref014","doi-asserted-by":"crossref","DOI":"10.1111\/jeu.12904","article-title":"Dense granule biogenesis, secretion, and function in Toxoplasma gondii","volume":"69","author":"MB Griffith","year":"2022","journal-title":"J Eukaryot Microbiol"},{"issue":"3","key":"ppat.1014212.ref015","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/mmi.14679","article-title":"Seizing control: How dense granule effector proteins enable Toxoplasma to take charge","volume":"115","author":"MW Panas","year":"2021","journal-title":"Mol Microbiol"},{"issue":"4","key":"ppat.1014212.ref016","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2023.03.001","article-title":"Cryptosporidium uses multiple distinct secretory organelles to interact with and modify its host cell","volume":"31","author":"A Gu\u00e9rin","year":"2023","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1014212.ref017","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1038\/s41467-025-60088-7","article-title":"SKSR1 identified as key virulence factor in Cryptosporidium by genetic crossing","volume":"16","author":"W He","year":"2025","journal-title":"Nat Commun"},{"issue":"9","key":"ppat.1014212.ref018","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2021.07.002","article-title":"Cryptosporidium rhoptry effector protein ROP1 injected during invasion targets the host cytoskeletal modulator LMO7","volume":"29","author":"A Gu\u00e9rin","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"10","key":"ppat.1014212.ref019","doi-asserted-by":"crossref","first-page":"116315","DOI":"10.1016\/j.celrep.2025.116315","article-title":"Genetic crosses reveal genomic loci responsible for virulence in Cryptosporidium parvum infection","volume":"44","author":"S Shaw","year":"2025","journal-title":"Cell Rep"},{"issue":"9","key":"ppat.1014212.ref020","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2025.07.024","article-title":"Cryptosporidium parvum multidrug resistance protein confers resistance to toxic gut microbial metabolite","volume":"33","author":"W Huang","year":"2025","journal-title":"Cell Host Microbe"},{"issue":"12","key":"ppat.1014212.ref021","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1038\/s41564-019-0539-x","article-title":"Life cycle progression and sexual development of the apicomplexan parasite Cryptosporidium parvum","volume":"4","author":"J Tandel","year":"2019","journal-title":"Nat Microbiol"},{"issue":"8015","key":"ppat.1014212.ref022","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41586-024-07466-1","article-title":"Transcriptional control of the Cryptosporidium life cycle","volume":"630","author":"KA Walzer","year":"2024","journal-title":"Nature"},{"issue":"12","key":"ppat.1014212.ref023","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1013847","article-title":"Small granule protein CP2 of Cryptosporidium translocates to the parasite-host interface during invasion and localizes to parasitophorous vacuole membrane in association with other secretory proteins","volume":"21","author":"F Yang","year":"2025","journal-title":"PLoS Pathog"},{"key":"ppat.1014212.ref024","doi-asserted-by":"crossref","unstructured":"Xiao R, Baptista RP, Agyabeng-Dadzie F, Li Y, Dong Y, Schmitz RJ. Deciphering transcription in Cryptosporidium parvum: polycistronic gene expression and chromatin accessibility. bioRxiv. 2025.","DOI":"10.1101\/2025.01.17.633476"},{"issue":"1","key":"ppat.1014212.ref025","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41467-024-44696-3","article-title":"Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum","volume":"15","author":"R Xu","year":"2024","journal-title":"Nat Commun"},{"key":"ppat.1014212.ref026","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.70451","article-title":"The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell","volume":"10","author":"JE Dumaine","year":"2021","journal-title":"Elife"},{"issue":"1","key":"ppat.1014212.ref027","doi-asserted-by":"crossref","first-page":"7749","DOI":"10.1038\/s41467-025-63012-1","article-title":"Targeted CRISPR screens reveal genes essential for Cryptosporidium survival in the 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Biol"},{"issue":"7561","key":"ppat.1014212.ref034","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature14651","article-title":"Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum","volume":"523","author":"S Vinayak","year":"2015","journal-title":"Nature"},{"issue":"1","key":"ppat.1014212.ref035","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41592-018-0238-1","article-title":"Imaging cellular ultrastructures using expansion microscopy (U-ExM)","volume":"16","author":"D Gambarotto","year":"2019","journal-title":"Nat Methods"},{"issue":"2","key":"ppat.1014212.ref036","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/mmi.13981","article-title":"Toxoplasma gondii TFP1 is an essential transporter family protein critical for micronemematuration And exocytosis","volume":"109","author":"PM Hammoudi","year":"2018","journal-title":"Mol Microbiol"},{"issue":"4","key":"ppat.1014212.ref037","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/j.1550-7408.1985.tb03106.x","article-title":"Ultrastructure of Cryptosporidium parvum oocysts and excysting sporozoites as revealed by high resolution scanning electron microscopy","volume":"32","author":"DW Reduker","year":"1985","journal-title":"J Protozool"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1014212","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:49:55Z","timestamp":1780681795000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014212"}},"subtitle":[],"editor":[{"given":"Mattie Christine","family":"Pawlowic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014212","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]}}}